Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex

Cognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature and largely accepted in the rodent literature because mPFC damage...

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Main Authors: Eun Hye Park, Kally C O'Reilly Sparks, Griffin Grubbs, David Taborga, Kyndall Nicholas, Armaan S Ahmed, Natalie Ruiz-Péreza, Natalie Kim, Simon Segura-Carrillo, André A Fenton
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Language:English
Published: eLife Sciences Publications Ltd 2025-06-01
Series:eLife
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Online Access:https://elifesciences.org/articles/104475
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author Eun Hye Park
Kally C O'Reilly Sparks
Griffin Grubbs
David Taborga
Kyndall Nicholas
Armaan S Ahmed
Natalie Ruiz-Péreza
Natalie Kim
Simon Segura-Carrillo
André A Fenton
author_facet Eun Hye Park
Kally C O'Reilly Sparks
Griffin Grubbs
David Taborga
Kyndall Nicholas
Armaan S Ahmed
Natalie Ruiz-Péreza
Natalie Kim
Simon Segura-Carrillo
André A Fenton
author_sort Eun Hye Park
collection DOAJ
description Cognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature and largely accepted in the rodent literature because mPFC damage causes deficits in tasks that may require cognitive control, as inferred, typically from the task design. In prior work, we used an active place avoidance task where a rat or mouse on a rotating arena is required to avoid the stationary task-relevant locations of a mild shock and ignore the rotating task-irrelevant locations of those shocks. The task is impaired by hippocampal manipulations, and the discharge of hippocampal place cell populations judiciously alternates between representing stationary locations near the shock zone and rotating locations far from the shock zone, demonstrating cognitive control concurrently in behavior and the hippocampal representation of spatial information. Here, we test whether rat mPFC lesion impairs the active place avoidance task to evaluate two competing hypotheses, a ‘central-computation’ hypothesis that the mPFC is essential for the computations required for cognitive control and an alternative ‘local-computation’ hypothesis that other brain areas can perform the computations required for cognitive control, independent of mPFC. Ibotenic acid lesion of the mPFC was effective, damaging the cingulate, prelimbic, and infralimbic cortices. The lesion also altered the normal coordination of metabolic activity across remaining structures. The lesion did not impair learning to avoid the initial location of shock or long-term place avoidance memory, but impaired avoidance after the shock was relocated. The lesion also did not impair the alternation between task-relevant and task-irrelevant hippocampal representations of place information. These findings support the local-computation hypothesis that computations required for cognitive control can occur locally in brain networks independently of the mPFC.
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spelling doaj-art-f8d6b8efea3a46bdbc906dc67e8eec282025-08-20T03:47:21ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011310.7554/eLife.104475Cognitive control of behavior and hippocampal information processing without medial prefrontal cortexEun Hye Park0https://orcid.org/0000-0001-9180-7579Kally C O'Reilly Sparks1Griffin Grubbs2David Taborga3Kyndall Nicholas4Armaan S Ahmed5Natalie Ruiz-Péreza6Natalie Kim7Simon Segura-Carrillo8https://orcid.org/0000-0001-8287-5158André A Fenton9https://orcid.org/0000-0002-5063-1156Center for Neural Science, New York University, New York, United States; Psychiatry, Columbia University Irving Medical Center, New York State Psychiatric Institute, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United States; Tandon School of Engineering, New York University, New York, United StatesCenter for Neural Science, New York University, New York, United States; Neuroscience Institute at the New York University Langone Medical Center, New York, United StatesCognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature and largely accepted in the rodent literature because mPFC damage causes deficits in tasks that may require cognitive control, as inferred, typically from the task design. In prior work, we used an active place avoidance task where a rat or mouse on a rotating arena is required to avoid the stationary task-relevant locations of a mild shock and ignore the rotating task-irrelevant locations of those shocks. The task is impaired by hippocampal manipulations, and the discharge of hippocampal place cell populations judiciously alternates between representing stationary locations near the shock zone and rotating locations far from the shock zone, demonstrating cognitive control concurrently in behavior and the hippocampal representation of spatial information. Here, we test whether rat mPFC lesion impairs the active place avoidance task to evaluate two competing hypotheses, a ‘central-computation’ hypothesis that the mPFC is essential for the computations required for cognitive control and an alternative ‘local-computation’ hypothesis that other brain areas can perform the computations required for cognitive control, independent of mPFC. Ibotenic acid lesion of the mPFC was effective, damaging the cingulate, prelimbic, and infralimbic cortices. The lesion also altered the normal coordination of metabolic activity across remaining structures. The lesion did not impair learning to avoid the initial location of shock or long-term place avoidance memory, but impaired avoidance after the shock was relocated. The lesion also did not impair the alternation between task-relevant and task-irrelevant hippocampal representations of place information. These findings support the local-computation hypothesis that computations required for cognitive control can occur locally in brain networks independently of the mPFC.https://elifesciences.org/articles/104475executive controllearningdecisionneural coordinationmemoryhippocampus
spellingShingle Eun Hye Park
Kally C O'Reilly Sparks
Griffin Grubbs
David Taborga
Kyndall Nicholas
Armaan S Ahmed
Natalie Ruiz-Péreza
Natalie Kim
Simon Segura-Carrillo
André A Fenton
Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
eLife
executive control
learning
decision
neural coordination
memory
hippocampus
title Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
title_full Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
title_fullStr Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
title_full_unstemmed Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
title_short Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
title_sort cognitive control of behavior and hippocampal information processing without medial prefrontal cortex
topic executive control
learning
decision
neural coordination
memory
hippocampus
url https://elifesciences.org/articles/104475
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